PMID- 33739786
OWN - NLM
STAT- MEDLINE
DCOM- 20210510
LR  - 20210510
IS  - 1532-0979 (Electronic)
IS  - 0147-5185 (Linking)
VI  - 45
IP  - 5
DP  - 2021 May 1
TI  - HER-2 Amplification in Uterine Serous Carcinoma and Serous Endometrial 
      Intraepithelial Carcinoma.
PG  - 708-715
LID - 10.1097/PAS.0000000000001682 [doi]
AB  - Human epidermal growth factor receptor 2 (HER-2) targeted therapy shows promising 
      results in HER-2-positive uterine serous carcinoma (USC). HER-2 scoring criteria 
      for USC and its associated noninvasive lesion, serous endometrial intraepithelial 
      carcinoma (SEIC), are not well-established. Here, we compare the breast and 
      gastric (GI) HER-2 immunohistochemistry (IHC) scoring criteria for HER-2 with 
      HER-2/neu fluorescence in situ hybridization (FISH) in 68 tumors (17 USC with 
      SEIC, 30 USC, 18 SEIC, 3 metastatic USC). The majority (97%) of lesions displayed 
      intratumoral HER-2 IHC heterogeneity. Breast or GI IHC scoring criteria were 
      performed equivalently. The breast and GI IHC criteria classified 51% and 47% USC 
      as HER-2 negative (IHC 0/1+), 40% and 45% as equivocal (IHC 2+), and 9% each as 
      HER-2 positive (IHC 3+). A quarter of USC classified as HER-2 negative or 
      positive with the breast (25%, n=7/28) or GI IHC criteria (23%, n=6/26) was 
      discordant by FISH. Specifically, 13% to 14% of IHC 0/1+ USC were FISH amplified; 
      50% of IHC 3+ USC were FISH negative. The majority (77% to 83%) of SEIC were 
      HER-2 IHC 0/1+, and no SEIC was HER-2 IHC 3+. A minority (4% to 7%) of IHC 0/1+ 
      SEIC were FISH positive. Discordant HER-2 status was observed between half 
      (47%,bn=7/15) of synchronous SEIC and USC. In conclusion, USC displays HER-2 
      intratumoral heterogeneity, a high IHC/FISH discordance rate, and variation in 
      HER-2 status between the SEIC and invasive components. Caution is required when 
      evaluating HER-2 in small biopsies, which should be repeated on excisions. Both 
      IHC and FISH should be performed on USC until clinical trials correlate HER-2 
      status with clinical response to HER-2-targeted therapy.
CI  - Copyright (c) 2021 Wolters Kluwer Health, Inc. All rights reserved.
FAU - Banet, Natalie
AU  - Banet N
AD  - Department of Pathology and Laboratory Medicine, Women & Infants Hospital and the 
      Warren Alpert Medical School of Brown University, Providence, RI.
FAU - Shahi, Maryam
AU  - Shahi M
AD  - Department of Pathology, The Mayo Clinic, Rochester, MN.
FAU - Batista, Denise
AU  - Batista D
AD  - Departments of Cytogenetics.
FAU - Yonescu, Raluca
AU  - Yonescu R
AD  - Departments of Cytogenetics.
FAU - Tanner, Edward J
AU  - Tanner EJ
AD  - Department of Obstetrics and Gynecology, Northwestern University, Feinberg School 
      of Medicine, Chicago, IL.
FAU - Fader, Amanda N
AU  - Fader AN
AD  - Gynecology and Obstetrics.
FAU - Cimino-Mathews, Ashley
AU  - Cimino-Mathews A
AD  - Pathology.
AD  - Oncology, The Johns Hopkins University and Hospital, Baltimore, MD.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Surg Pathol
JT  - The American journal of surgical pathology
JID - 7707904
RN  - 0 (Biomarkers, Tumor)
RN  - EC 2.7.10.1 (ERBB2 protein, human)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
MH  - Biomarkers, Tumor/*genetics
MH  - Biopsy
MH  - Carcinoma in Situ/*genetics/pathology
MH  - Endometrial Neoplasms/*genetics/pathology
MH  - Female
MH  - *Gene Amplification
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Neoplasms, Cystic, Mucinous, and Serous/*genetics/pathology
MH  - Predictive Value of Tests
MH  - Receptor, ErbB-2/*genetics
MH  - Reproducibility of Results
MH  - Uterine Neoplasms/*genetics/pathology
COIS- Conflicts of Interest and Source of Funding: Support was provided to facilitate 
      this research from Genentech (A.C.-M.) and the Dr Susan Burgert Research 
      Endowment (A.N.F.). A.C.-M. receives grant funding from Bristol-Myers Squibb and 
      is a paid consultant for Bristol-Meyers Squibb and Roche Diagnostics. The 
      remaining authors have disclosed that they have no significant relationships 
      with, or financial interest in, any commercial companies pertaining to this 
      article.
EDAT- 2021/03/20 06:00
MHDA- 2021/05/11 06:00
CRDT- 2021/03/19 14:03
PHST- 2021/03/20 06:00 [pubmed]
PHST- 2021/05/11 06:00 [medline]
PHST- 2021/03/19 14:03 [entrez]
AID - 00000478-202105000-00013 [pii]
AID - 10.1097/PAS.0000000000001682 [doi]
PST - ppublish
SO  - Am J Surg Pathol. 2021 May 1;45(5):708-715. doi: 10.1097/PAS.0000000000001682.